Method and apparatus for detecting amine producing organisms in the vagina

ABSTRACT

A method of detecting pathogenic bacteria in the vagina, includes providing a vaginal moisture receiver receivable into the vagina; providing a reactant which changes color when contacted by moisture containing pathogenic bacteria; receiving vaginal moisture on the receiver; and contacting reactant with vaginal moisture on the receiver, whereby a change in color at the receiver indicates the presence of pathogenic bacteria.

BACKGROUND OF THE INVENTION

This application is a continuation-in-part of prior U.S. applicationSer. No. 08/789,484 filed Jan. 27, 1997, now U.S. Pat. No. 5,827,200 andthis application is also a continuation-in-part of prior U.S.application Ser. No. 09/072,257 filed May 4, 1998, now U.S. Pat. No.6,013,036 which is a continuation-in-part of prior U.S. application08/890,748 filed Jul. 11, 1997 now U.S. Pat. No. 5,916,176 which is acontinuation-in-part of prior U.S. application Ser. No. 08/699,251 filedAug. 19, 1996, now U.S. Pat. No. 5,735,801, which is acontinuation-in-part of prior U.S. application Ser. No. 08/570,534 filedDec. 11, 1995, now U.S. Pat. No. 5,762,614 which is acontinuation-in-part of prior U.S. application Ser. No. 08/537,379 filedOct. 27, 1995, now U.S. Pat. No. 5,577,512, which is acontinuation-in-part of prior U.S. application Ser. No. 08/376,830 filedJan. 23, 1995, now U.S. Pat. No. 5,664,579, which is acontinuation-in-part of prior U.S. application Ser. No. 08/295,399 filedAug. 25, 1994, now U.S. Pat. No. 5,425,377 and a continuation-in-part ofprior U.S. Application Ser. No. 08/789,835 filed Jan. 31, 1997, now U.S.Pat. No. 5,782,801.

This invention relates generally to detection of bacteria in moisture,and more particularly to method and apparatus for easily and quicklytesting for the presence of bacteria in moisture samples from thevagina. and a continuation-in-part of prior U.S. application Ser. No.08/789,835 filed Jan. 31, 1997, now U.S. Pat. No. 5,782,801.

There is need for simple, easily used apparatus for reliably and quicklyobtaining indications of bacteria, as for example pathogenic bacteria,in moisture samples, for example which are obtainable from the vagina.There is also need for simple, effective methods to obtain suchindications. Prior apparatus and techniques were cumbersome, and lackedthe unusual advantages disclosed herein.

SUMMARY OF THE INVENTION

It is a major object of the invention to provide improvements in methodand apparatus meeting the above needs. Basically, the method of theinvention includes the following steps:

a) providing a vaginal moisture receiver receivable into the vagina,

b) providing a reactant which changes color when contacted by moisturecontaining pathogenic bacteria,

c) receiving vaginal moisture on the receiver,

d) and contacting the reactant with vaginal moisture on the receiver,

e) whereby a change in color at the receiver indicates the presence ofpathogenic bacteria.

In one form of the invention, the reactant is carried by the receiver,which may be in the form of a swab. The swab may be carried on anelongated carrier such as a stick, enabling ready manipulation of thereceiver or swab, to control contacting of the reactant with vaginalmoisture on the receiver or swab. The reactant may advantageouslycomprise potassium hydroxide, and the latter may be in distributed form,such as powder, on or in the receiver or swab, or may be in aqueoussolution, such as 10 to 20% potassium hydroxide on the receiver.

The present invention eliminates need for rubbing of retrieved vaginalmoisture as onto a solid state reactant surface located for example onan auxiliary plate, whereby the present invention substantiallysimplifies the testing method and equipment employed to detect thepresence of pathogenic bacterial in the vagina. The present inventionalso eliminates need for a "whiff" test or odor test for pathogenicbacteria , as is commonly in use.

In another form of the invention the reactant is brought into contactwith vaginal moisture on the receiver or swab, after that moisture isretrieved. For example, the reactant may be carried to flow into contactwith the receiver, such as a swab or other form, or the reactant may besprayed onto the receiver, to contact the retrieved vaginal moisture, toenable a visible color change at the receiver if pathogenic bacteria arepresent. The reactant in flowable or otherwise applicable distributedform may be otherwise placed onto the receiver. In this regard, thereactant may be provided in flowable form in a container, and may becaused to flow from the container into contact with the receiver.

Another form of the method includes

a) providing an elongated carrier and a flexible outer containersupported on the carrier,

b) providing the receiver such as a swab on the carrier to communicatewith the interior of the outer container,

c) providing a frangible inner container protectively located within theouter container, and providing flowable aqueous alkaline fluid reactantwithin the inner container,

d) and exerting pressure on the outer container sufficient to rupturethe inner container, thereby releasing the reactant into the interior ofthe outer container to enable reactant fluid flow to said receiver forreaction with bacteria contained in vaginal moisture on the receiver.Such reactant may consist essentially of a dilute aqueous solution ofpotassium hydroxide. That solution may consist of 10 to 20% potassiumhydroxide.

The invention further contemplates providing pH detection means fordetection of vaginal moisture pH in conjunction with performing thesteps referred to above. The pH detection means may be provided at onelocation on a carrier, such as a stick, and remotely from the vaginalmoisture receiver referred to that is used to detect for pathogenicbacteria.

Apparatus for use in detecting pathogenic bacteria may include:

a) an elongated assembly including an elongated carrier and a flexibleouter container supported on the carrier,

b) a vaginal moisture absorbing swab at one end of the assembly tocommunicate with the interior of the outer container,

c) a frangible inner container protectively located within the outercontainer, and a flowable aqueous alkaline fluid reactant within theinner container,

d) whereby pressure exerted on the outer container sufficient to rupturethe inner container, releases the reactant into the interior of theouter container to enable reactant fluid flow to the swab for reactionwith bacteria containing vaginal moisture absorbed into the swab, and acolor change of the swab may be observed as indicative of the presenceof pathogenic bacteria.

The outer container may be located in close association with the swab,such as between the end of a carrier stick and the swab itself, wherebythe reactant fluid when released into the outer container interior isdirectly accessible to the swab and to the bacteria carrying moisturesample. Alternatively, the outer container may be provided on thecarrier at a location relatively remote from the swab. In that event aduct may be provided to be associated with the carrier to convey fluidreactant from the container interior to the swab. Controllable manualpressure on the outer container, after breakage of the inner container,controls flow of the reactant fluid to the swab.

Yet another object is to employ bending or manual pressure exertion onthe outer container to flex its wall or walls for pressurizing the innercontainer to break its wall. The outer container may consist of plastic,and the inner container of thin walled glass, i.e. it is frangible.

Yet another step is to manipulate the assembly to cause the outercontainer to exert endwise and sidewise force on the swab to cause theswab to absorb vaginal moisture, in the vagina.

These and other objects and advantages of the invention, as well as thedetails of an illustrative embodiment, will be more fully understoodfrom the following specification and drawings, in which:

DRAWING DESCRIPTION

FIG. 1 is a view showing use of an elongated assembly;

FIG. 2 is an enlarged section taken lengthwise through an end portion ofthe FIG. 1 assembly;

FIG. 3 is a view like FIG. 2, showing manual fracture or rupture of aninner container located within an outer container, as also seen in FIG.2;

FIG. 4 is a view like FIG. 3, showing liquid from the inner containerhaving been released into the interior of the outer container;

FIG. 5 is a view like FIG. 4, the liquid having flowed from the interiorof the outer container to a swab at the end of the assembly, for mixingwith vaginal moisture in the swab;

FIG. 6 is a view like FIG. 2, showing a modification;

FIG. 7 is an enlarged view of a pH detection means on a carrier, such asis also shown in FIG. 1;

FIG. 8 is a side view showing a modification;

FIG. 9 is a side elevational view of stick apparatus incorporating theinvention;

FIG. 10 is an enlarged side view of one end portion of the FIG. 9 stickapparatus;

FIG. 11 is an enlarged section taken on lines 11--11 of FIG. 10;

FIG. 12 is an enlarged end view taken on lines 12--12 of FIG. 10;

FIG. 13 is an elevation, partly in section, showing a modification;

FIG. 14 is a side elevation of the FIG. 13 modification;

FIG. 15 is an end view taken on lines 15--15 of FIG. 14;

FIG. 16 is an elevation showing a further modification;

FIG. 17 is an elevation showing yet another modification;

FIG. 18 is a view like FIG. 10 showing a protective porous layer appliedover a pH indicator strip;

FIG. 19 is a view like FIG. 18, but showing the protective layer alsoapplied over the color comparison measurement means;

FIG. 20 is a view like FIG. 16, showing a protective porous layerapplied over a pH indication strip;

FIG. 20a is a view like FIG. 20, but showing the protective porous layerextending over the color comparison measurement means;

FIG. 21 is a perspective view showing pH indictor manipulation manually;

FIG. 22 is a plan view of the top side of a modified stick apparatus;

FIG. 23 is a plan view of the bottom side of the FIG. 22 stickapparatus;

FIG. 24 is an edge view taken on lines 24--24 of FIG. 22;

FIG. 25 is an end view taken on lines 25--25 of FIG. 24;

FIG. 26 is a plan view of modified apparatus;

FIG. 27 is an enlarged section taken on lines 27--27 of FIG. 26;

FIGS. 28 and 29 are side and top views of carrier and treatmentapparatus, in generally useful form;

FIGS. 30 and 31 are like FIGS. 28 and 29 and show modified carrier andtreatment apparatus;

FIG. 32 is an elevation showing a swab on a receiver, displaying a localchange in color;

FIG. 33 is like FIG. 32 but indicating bringing of a reactant intocontact with the swab;

FIG. 33a is like FIG. 33, but showing spraying of the reactant onto theswab;

FIG. 33b is like FIG. 33 but showing flowing of the reactant onto theswab.

DETAILED DESCRIPTION

FIG. 32 illustrates a method of detecting pathogenic bacteria in thevagina. The steps of the preferred method include

a) providing a vaginal moisture receiver receivable into the vagina,

b) providing a reactant which changes color when contacted by moisturecontaining pathogenic bacteria,

c) receiving vaginal moisture on the receiver,

d) and contacting the reactant with vaginal moisture on the receiver,

e) whereby a change in color at the receiver indicates the presence ofpathogenic bacteria.

As shown, the receiver may advantageously comprise a swab 400, mountedor carried as at one end of a carrier stick 401, and the color changingreactant may be incorporated on, or in the interstices of the receiverswab. When the reactant is contacted by vaginal moisture, a change incolor at the receiver indicates the presence of pathogenic bacteria,such color change indicated by shading at 402. The reactant may consistof potassium hydroxide and may be distributed as in powder form in theswab. The receiver is typically manipulated to control contact of the insitu reactant with vaginal moisture on the receiver.

In a modified form of the method, the reactant is brought into contactwith the swab on which vaginal moisture has been deposited as duringswab use, i.e. swabbing. For example, FIG. 33 shows a swab 400a free ofreagent during swabbing, but on which vaginal moisture has beendeposited. Reagent is brought into contact with the moisture on theswab, as indicated by the arrow 403. The shaded area 402 indicates achange in color at the receiver or swab, showing presence of pathogenicbacteria. Arrow 403 may represent placement of the reactant onto theswab.

Another example of such contacting is spraying of the reactant insprayable form onto the swab, as shown at 403a in FIG. 33a. The spray404 discharges from a spraying device 405. A further example of suchcontacting is flowing of the reactant, in fluid form, indicated by arrow406 in FIG. 33b, onto the swab, to contact vaginal moisture. The fluidreactant discharges from a fluid container 407, which may for example befree of the carrier stick 401, or which may be mounted on the carrierstick as at 407a. See for example FIGS. 2-6 and their associateddescription herein. Flow from 407a is indicated at 408.

Steps of the method of FIG. 33b may typically include the following,with extended references to FIGS. 2-5 herein:

a) providing an elongated carrier and a flexible outer containersupported on the carrier,

b) providing the receiver such as a swab on the carrier, to communicatewith the interior of the outer container,

c) providing a frangible inner container protectively located within theouter container, and providing flowable aqueous alkaline fluid reactantwithin the inner container,

d) and exerting pressure on the outer container sufficient to rupturethe inner container, thereby releasing the reactant into the interior ofthe outer container to enable reactant fluid flow to the receiver forreaction with bacteria in or on vaginal moisture on the receiver.

The flowable reactant may consist of a aqueous solution of potassiumhydroxide as for example 10 to 20% potassium hydroxide.

The carrier stick may also carry other testing elements (indicated at410 in FIGS. 33, 33a and 33b) to test or detect other conditions in thevagina. See for example FIGS. 7-31 herein and their associateddescriptions.

FIGS. 28 and 29 show a preferred apparatus for detecting first andsecond conditions in the vagina or urethra. Such apparatus includeselements in combination, comprising:

a) an elongated carrier insertible endwise into the vagina,

b) first structure at a first location on the carrier for use indetecting said first condition,

c) and second structure at a second location on the carrier for use indetecting said second condition,

d) portions of the first and second structures being inserted into thevagina or urethra, by manipulation of the carrier, and to besubsequently withdrawn, for use in detecting such conditions.

The first structure 300 may be a pH detection means, as described below,and the second structure 301 may be a pathogenic bacteria detectionmeans. Incorporation of both and at opposite ends of a common carrier302, such as a stick, facilitates rapid testing of two conditions, bythe user, at essentially one time, as well as ease of testing. Thesecond structure 301 may include a reactant container on the carrier,and positioned for allowing contact of reactant with vaginal or urethralmoisture on that portion of the second means insertible into the vaginaor urethra; and as referred to, the portion of the second meansinsertible into the vagina or urethra may include a swab 301a forcollecting vaginal moisture.

FIGS. 30 and 31 are the same as FIGS. 28 and 29, but incorporate a thirdstructure 303 on the carrier between 300 and 301, to provide release ofa secondary odor corresponding to a primary odor created during use ofthe second structure, for odor comparison purposes. The third structuremay include a cover 303a releasably adherent to the carrier, and asecondary odor source substance 303b in a pocket 303c on the carrierconcealed by said cover. After removal of the cover, the user canrapidly compare the odors from source 303b and from the second structure301 to determine presence of pathogenic bacteria.

More particularly, and in FIG. 1, an elongated assembly 10 is shown toinclude an elongated carrier 11 such as a stick, (corresponding to 302)and a swab 12 (corresponding to swab 301a) as for example a sponge, orother porous material, at the forward end of the assembly. The swab isused to absorb moisture from the vaginal cavity 13, during use of theassembly. FIG. 1 shows a user's finger and thumb 20 and 21 manipulatingthe assembly.

Controllable test liquid supply means is provided at 14, between theforward end of the carrier 11 and the swab 12. The means 14 is adaptedto be manually squeezed to effect controllable communication ofcontained test liquid to the swab 12, for reaction with vaginal moisturepicked up by the swab. Since the supply means or unit 14 is locatedbetween 11 and 12, it provides a test means incorporated in or on theassembly 10.

FIG. 2 shows the means or unit (corresponding to 301) as incorporatingan outer container 16 which is elongated and tubular, having cylindricalside wall 17, and end wall 18 attached to the forward end of carrier 11.The interior 19 of the container communicates with swab 12, and for thispurpose the swab may be received into the open forward end portion 17aof the outer container, thereby mounting the swab to the container.

A frangible inner container 24 is located within the interior 19 ofcontainer 16, and may be elongated, as shown. Container 24 may consistof a hollow, thin-walled glass capsule to contain test liquid 25. Theouter container side wall 17 may consist of relatively stiff plasticmaterial, which is sufficiently flexible to be bent or squeezed, as byor between user's finger and thumb 20 and 21, as seen in FIG. 3. Suchbending or squeezing, exerting pressure on the outer container, issufficient to rupture the inner container as seen in FIG. 3, therebyreleasing contained reactant test liquid 25 into the interior 19 of theouter container. See FIG. 4. This provides for controlled access of thetest liquid to the swab, for reaction with the vaginal moisture, as seenin FIG. 5. See orientation of the assembly 10 to cause gravitation ofthe test liquid to flow into contact with the end of the swab carried bythe forward end portion of the outer container.

In one form of the invention, the test liquid consists of dilute aqueousalkaline liquid for reaction, as with bacteria in the vaginal moisturein the swab. Such bacteria may be pathogenic. One example of thealkaline test liquid is a 10% to 20% aqueous solution of potassiumhydroxide. When such solution contacts amines resulting from bacterialactivity, a characteristic odor is produced, as by formation of gaseousamines such as cadaverine and/or putrescine indicated at 49. The usermay thereby quickly and efficiently determine the existence of bacteriasuch as pathogenic bacteria in the vaginal moisture, using a simpleunitary test means and procedure as described.

FIG. 6 shows a modification in which the test liquid supply means 14" islike 14, but located and supported at the opposite end of the carrier11". A duct 50 is provided in the carrier to communicate the releasedliquid to the swab 12". The user can manipulate the stick and swab, andalso control test liquid delivery to the swab, from the remote orexternal end of the carrier. Note the reduced diameter of the carrier.

FIG. 7 shows provision of a pH detection means as described in U.S. Pat.Nos. 5,577,512; 5,425,377; and 5,735,801 incorporated herein byreference. Such detection means corresponds to that indicated at 300 inFIG. 28.

As shown in FIG. 7, a first means 111 may comprise a pH indicationstrip, such as a Nitrazine® Phenaphthazine strip, wound about the stickor carrier end portion 110a and adhered to same as by an adhesive. Acolor comparison pH measurement means 112 may comprise a thin paperstrip adhered to the stick surface to extend lengthwise of the stickfrom the edge or end 111a of the first means 11. The stick showncorresponds to stick 302 of FIG. 28. A second means is shown to havecolor gradations in a series sequence, as in colored bands 112apositioned lengthwise of or along the stick. In addition, the paperstrip 112 may include pH numerical indicators 112b along side the colorgradation bands, to enable:

visual color comparison of the pH indication means 111 (immediatelyafter its exposure to vaginal fluid) with the bands 112a, for visualselection of that band most close in color to the color of theindication means 111; and immediate visual readout of the pH numberadjacent the selected band.

The stick projects freely at 110c away from the first and second means111 and 112 for manual manipulation to first obtain pH indication ofvaginal moisture at one end of the stick, and to enable visualinterpretation of that indication by color comparison with the secondmeans, without manual release of the stick. The stick or carrier is thenused to obtain a test for bacteria presence in vaginal fluid, asdescribed above. The stick is then disposable, or may be disposed of,after a swabbing step to be described.

FIG. 8 shows another form of the invention, elements of which correspondto elements of FIGS. 1-7 bearing the same identifying numerals.

In FIG. 8, the outer container has porous means associated therewith, tocommunicate with the interior of the outer container. The provision ofsuch porous means enables reactant flow of reactant fluid directlyreleased from the fractured inner container into the porous means forreaction with vaginal moisture absorbed into the porous means.Accordingly, flow of reactant fluid to a separate area spaced endwisefrom the container is not required.

As shown, part or all of the outer container 50 defines an associatedporous means, as in the form of a wall 50a consisting of flexible wovenmaterial located for example at the end of the assembly. The wovenmaterial may consist of synthetic or non-synthetic material, closelywoven in a warp and woof pattern, and may include stiffener meansassociated therewith to assist in maintaining the tubular shape of theouter container. See for example stiffener elements 52.

When squeezed, the outer container deflects to transmit force to theinner container 24 to fracture its wall. This effects release of thereactant fluid into the interior 19 of the outer container and directaccess of said reactant fluid to vaginal moisture absorbed intointerstices formed by porous means which may be defined by the outercontainer or part thereof. Such squeezing of the outer container alsotends to displace moisture therein toward the reactant fluid, forreaction therewith as described above. A more direct testing method isthereby provided.

The fluid capsule 24 may contain a dye of such color as to make it clearthat the fluid in capsule 24 has permeated the sponge 12 or woven cover52a, during use. Usable dyes include

Methylene Blue USP 1% (10 mg/ml) NDC 0517-0373-70

Indigo Carmine 0.8% solution NDC 0517-0375-10

Both dyes are approved for IM or IV use by the U.S. Food and DrugAdministration.

The test liquid released from the inner container may be used to reactwith vaginal moisture absorbed by or on the porous means 12, fordetection of estrogen level. See in this regard my pending applicationSer. No. 08/570,534, filed Dec. 11, 1995, and U.S. Pat. No. 5,735,801,incorporated herein by reference.

As referred to, use of the means 300 at the opposite end of the stickconcerns determining need for estrogen replacement therapy, or estrogenor estradiol dose change, through vaginal wall moisture pH determinationor urethral wall moisture pH determination. Typical steps of such usageinclude:

a) determining local acidity proximate a moist wall surface of thevagina or urethra, as differing from desired threshold level, as in thesubstantial absence of bacterial vaginosis, or other contaminants suchas medication, blood, semen,

b) and administering sufficient estrogen or estradiol to result inchange in said acidity toward said level.

A more complete method includes:

a) first determining local acidity proximate a moist wall surface of thevagina, said determining employed as an indicator of the presence orabsence of bacterial vaginosis,

b) and, after a vaginosis condition has been treated and eliminated,then again determining local acidity proximate a moist wall surface ofthe vagina, as differing from desired threshold level,

c) and administering sufficient estrogen or estradiol to result inchange in said acidity toward said threshold level.

A pH indicator 100, as seen in FIG. 21 may be employed, and thatindicator may be located at one end of a carrier 101, like carrier 302which is easily manipulable into contact with the vaginal or urethralwall, shown at 102, (after or before use of device 301) the user'sfinger shown at 103 to urge the tissue strip toward the wall surface.Such an indicator may take the form of one of the following, althoughother indicators are usable.

i) NITRAZINE® paper

ii) phenaphthazine on a carrier

iii) a material or materials exhibiting different colorations or otherindicators as a function of pH level.

The indicator may desirably exhibit different colorations or changescorresponding to different pH levels, of moisture at the vaginal orurethral wall, and from which the observed coloration or changes may beused to indicate need for greater or lesser estrogen or estradioldosage, as on a daily or other periodic basis. In the case of NITRAZINE®paper (phenaphtazine), the correlation of pH to color is as follows:

    ______________________________________                                        pH                 Color                                                      ______________________________________                                        4.5                golden yellow                                              5.0                                beige                                      5.5                                light olive                                6.0                                dark olive                                 6.5                                olive blue                                 7.0                                purple blue                                7.5                                dark blue                                  ______________________________________                                    

In a typical example, if the user detected or determined an indicatorcolor of dark olive, it would be determined that an estrogen orestradiol increase above the existing daily level of use would berecommended, in order to diminish pH level to 4.2 to 4.5 within one totwo weeks, for example. Testing would be performed on a once a weekbasis. Thus, if the user had been taking 1 mg. of estrogen or estradiolper day, for example orally, she would be recommended to increase thatlevel to 1.5 mg. per day, the objective being to reduce the pH level toabout 4.5 within about 10-21 days. If the tested color were not goldenyellow (4.5 pH) after 7-8 days, the dosage might be increased to 2.0 mg.level, per day, until a goldenrod yellow color of the test strip wasachieved. Thus, pH determination is indicative of need for change inestrogen or estradiol dosage (up or down).

In FIGS. 9-12, an elongated, narrow carrier stick 10' may consist ofwood, plastic, or other material. Provided on the carrier stick are:

a pH indication means, as generally shown at 11', at one end portion10a' of the stick; and

a color comparison pH measurement means, as generally indicated at 12',spaced from stick end portion 10a', but close to 11';

As shown, the first means 11' may comprise a pH indication strip, suchas a NITRAZINE® (Phenaphthazine) strip, wound about the stick endportion 10a' and adhered to same as by an adhesive. NITRAZINE®(Phenaphthazine) strips are products of Bristol-Myers Squibb. The colorcomparison pH measurement means 12' may comprise a thin paper stripadhered to the stick surface to extend lengthwise of the stick from theedge or end 11a' of the first means 11'. The second means is shown tohave color gradations in a series sequence, as in colored bands 12a',positioned lengthwise of or along the stick. In addition, the paperstrip 12' may include pH numerical indicators 12b' along side the colorgradation bands, to enable:

visual color comparison of the pH indication means 11' (immediatelyafter its exposure to vaginal or urethral fluid or moisture) with thebands 12a', for visual selection of that band most close in color to thecolor of the indication means 11';

and immediate visual readout of the pH number adjacent the selectedband.

Such readout of pH is then compared with the desired level of about4.2-4.5 to enable determination of a recommended dosage of estrogen orestradiol, as on a daily basis.

The stick projects freely at 10c' away from the first and second means11' and 12' for manual manipulation (see the grasping finger and thumb18' and 19'), to first obtain pH indication of vaginal or urethral wallmoisture at one end of the stick, and to enable visual interpretation ofthat indication by color comparison with the second means, withoutmanual release of the stick. The stick is then disposable, or may bedisposed of.

Lengthwise spacing "d" between 12' and stick end 10d' is such as toenable free manual manipulation of the stick; and such spacing istypically between 3 and 5 inches, enabling ready finger grasping of thestick and manipulation thereof. In a specific example, "d" is about 4inches, and the stick diameter or width is about 3/16 to 3/8 inch. Seealso FIGS. 10-12.

The method of measuring pH of vaginal moisture includes the steps:

a) providing a pH indicator on a carrier stick,

b) manipulating the stick to obtain pH indication of vaginal or urethralwall moisture at said indicator,

c) visually interpreting that indication to determine need for a changein estrogen or estradiol dosage,

d) and disposing of the stick,

The overall sizes of 11', 12' and 13' are such as to enable readyinsertion into the vagina, or urethra, or application to a surface ofthe vagina or urethra, via stick manipulation at zone 10c'.

Referring now to the modification shown in FIGS. 13-15, a smoothsurfaced protective tip 20' is provided to face endwise at the end 10aa'of the stick end portion 10a'. As shown, the tip 20' is endwise convex,as for example bulbous, to provide for or enable comfortable insertionof the stick end portion 10a' into the vagina or urethra, for pHmeasurement. The tip 20' may typically be formed integrally with asleeve 20a' assembled over and closely fitting the measurement strip11', and may be suitably adhered thereto, locally, as at 21'. A suitablebonding agent is epoxy. The remainder of the strip 11' is thereforeavailable for pH indication. Alternatively, the sleeve may be attached,as by heat shrinking, or by wedge fit.

A fluid access opening is provided through the wall of the sleeve,whereby vaginal moisture or fluid may access the strip 11' via thatopening. See for example elongated slot 22' in the sleeve wall 20aa'.The sleeve and tip may consist of transparent, molded, plastic material,to facilitate viewing of a change of color of the strip 11.

In FIG. 16, the sleeve 20a' is shortened and attached at sleeve end 20a"into flush, or near flush, relation with the surface of the strip, at alocus on stick end portion 10a'. This leaves the remaining length 11f'of the strip openly exposed for moisture contact.

In FIG. 17, the sleeve 20a'" is also shortened and attached to the stickend portion 10a', and in endwise alignment with the strip 11'. This alsoleaves the remaining length 11f" of the strip openly exposed formoisture contact.

Referring now to the modification seen in FIG. 18, the elements the sameas in FIG. 10 are given the same numerals. In addition a protectivelayer 40' in the form of a thin porous barrier, is applied adjacent theouter side of strip 11' so as to cover the latter (i.e. extendthereabout) and to be carried by the stick. Layer 40' allows vaginalmoisture to penetrate through it and to contact the pH indicator strip11', as during a test. Following the test, the strip 11' may be observedas described above, and for this purpose the layer 40' may be at leastpartly removed from adjacency to the strip, as by complete manualremoval. Opposite end portions 40a' and 40b' of layer 40' may beinitially attached as by light bonding or sticking to the ends of thestrip 11', or to the stick, allowing pull-away removal of the layer atthe end of the test. Such bonding agents are known, as on 3M MicroporeTape. Layer 40' acts as a barrier, during a test, to block directcontact of vaginal tissue or urethral tissue with strip 11', preventingany possible irritation of such tissue.

In FIG. 19, the elongated layer 45' is like layer 40', but also extendsover and about the color comparison measurement means 12', and isadhered, as described above, to the elements 11' and 12', as at 45a' and45b' to completely cover 11' and 12' as during a test, while allowingpull-away of the layer 45' for visual observation of 11 and 12 after thetest. Either one or both of 11' and 12' may be considered as a pHdetecting means.

FIG. 20 is like FIG. 16, but layer 50' corresponding to layer 40' hasits end 50a' adhered to and about the sleeve 20a", while end portion50b' is adhered to the right end of strip 11', as shown. Note smoothsurfaced blunt knob 20', as referred to above.

FIG. 20a is like FIG. 20, except that the layer 60', corresponding to50', is elongated to cover the color comparison measurement means 12',and to adhere at 60b' to the rightward end of 12'.

In FIGS. 18-20a, the porous barriers, as at 40', 45', 50' and 60' mayconsist of one or more barrier tissue layers, as for example are used inincontinence pads. One example is the outer layer of the Kimberly Clarkproduct NEW DEPEND. Another usable barrier is the 3M product known asMICROPORE tape. One side of such tape is "tacky", i.e. weakly adhesive,so that it will adhere along the tape length to the elements 11' and/or12' referred to. Barriers 45' and 50' as referred to may comprise suchtape material.

In FIGS. 22-25, a modified elongated, narrow carrier stick 200 mayconsist of wood, plastic or other carrier material. A pH indicationstrip 201 such as phenaphthazine paper is adhered to one substantiallyflat side 200a of the stick 200, and near one end 200b, as by anadhesive. The strip 201 is elongated, and spaced from opposite edges200c and 200d of the stick, as well as from end 200b. Typically,rectangular strip width is about 0.25 inches, and its length is about1.5 inches. The stick width is about 0.375 inches, its length is about 5inches and its thickness is about 0.125 inches.

The stick edges 200c and 200d are convexly curved or rounded as at 210and 211 in FIG. 25. Also, the stick opposite ends 200f and 200g areconvexly curved or rounded as at 212 and 213.

The handle portion 200e of the stick is desirably textured, as byprovision of dimples 215 on side 200a of the stick. The length of suchtexturing may be about 1.5 inches, from end 200b. Such texturing aidsfinger and thumb gripping of the handle portion for accurate stickmanipulation to position strip 201 adjacent the vaginal wall. Aiding ofmanipulation of the paper strip is enhanced by locating the texturingand paper strip at the same side of the stick. Note that the stickpreferably has smooth top surface extent at 220 between 215 and 201, andalso a smooth bottom surface at 221. Stick 200 may be extended tosupport or carry bacteria test structure as at 301 described above. SeeFIG. 24. Such a stick may be received in a receptacle indicated at 230',and like receptacle 230 described above.

FIGS. 26 and 27 show yet another and preferred kit in which an indicatorstrip or tip 228 (corresponding to strip or tip 111) is carried at theleft end of elongated stick 229. A swab 233 is carried at the right endof the stick. An encapsulating, thin, flexible, transparent receptacle230 protectively contains the elongated stick, tip 228 and swab 233, andmay be torn open to retrieve the stick. The receptacle may consist ofthin walled plastic sheets 230a and 230b bonded together along sheetedge portions indicated at 250, 251, 252 and 253, whereby the receptacleis sealed.

A thin, elongated paper insert sheet 260 is also received in thereceptacle, to overlie most of stick 200, whereby use instruction andidentification data may be printed on the sheet 260 and presentedupwardly or outwardly for viewing through the transparent upper sheet230a. Sheet 260 defines a narrow window or cut-out at 261, which iselongated along a mid-portion 262 of sheet 260, as shown.

Color comparison elements such as bands are carried by the insert sheet260, as in two rows shown at 228a and 228b, at opposite sides of thewindow. Preferably, the longitudinally spaced bands extend to laterallyspaced edges of the window, for ease of color comparison of theindicator (after its exposure to moisture as described above) with thedifferent bands. Sheet 260 may be eliminated, and the bands printed oraffixed on the receptacle top sheet, to define the window.

Longitudinally spaced bands have different colors, while laterallyoppositely spaced bands have the same color. Note their pH numericallabeling, at 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, and 7.5, along the windowlength.

In use, the right end of the receptacle is opened, and the carrier stick229 is withdrawn, for use. Thereafter, the indicator tip 228, which maybe cylindrical, after its exposure to moisture, is reinserted into theelongated receptacle 230, under the insert sheet 260, to bring tip 228under the window 261. Tip 228 preferably has a width or diameter greaterthan the window width, so that it adjacently registers with thesuccessive bands in the two rows as the tip moves longitudinally. Thisfacilitates ease of color comparison use. The tip and stick remain inthe receptacle, for ease of disposal.

In addition to provision and manipulation of a first carrier stick asreferred to, with respect to vaginal or urethral moisture samples, themethod may also include providing an elongated second carrier having asecond pH detector on that carrier at an end position thereof, andmanipulating the second carrier to effect exposure of the seconddetector to vaginal or urethral moisture, thereby to cause the seconddetector to exhibit a color change, and comparing the color changesexhibited by the first and second detectors. If color changes exhibited(due to both vaginal and urethral moisture contact with the detector)are the same, a validity check is thereby provided.

Accordingly, the method of determining validity of pH of body moistureor fluid may include:

a) determining pH of vaginal moisture or fluid, by employment of a firstindicator,

b) also determining pH of urethral moisture or fluid, by employment of asecond indicator.

The two indicators may then be compared, as for example by comparison ofcolor changes produced on or by the indicators. The indicatorsthemselves would be identical as to color change capability.

If a stick as in FIG. 24 is used, or a similar stick, its opposite endcan easily be used to determine presence of pathologic bacteria.

EXAMPLES

OBJECTIVES:

To confirm the elevation of vaginal pH expected in patients withbacterial vaginosis and to examine the relationship of serum FSH andestradiol levels to vaginal pH in normal patients without vaginosis.

STUDY DESIGN:

2,038 patients in a solo private practice underwent measurement ofvaginal pH during routine pelvic examinations. 201 of these patientswere chosen at random for this study. Measurements were made of serumlevels of FSH and estradiol. Vaginal cultures were taken from 83patients. Specimens were sent to a single commercial laboratory. VaginalpH was determined by phenaphthazine (NITRAZINE®) pH paper. Vaginal pHwas correlated with serum FSH, estradiol levels, and vaginal culturesusing statistical analysis.

RESULTS:

Vaginal pH was elevated in patients with documented vaginosis. Serumestradiol levels showed an inverse and serum FSH levels showed a directstatistical correlation with vaginal pH.

MATERIALS AND METHODS:

Between May 1995 and May 1996, 2,038 patients in a private gynecologicpractice were tested for vaginal pH. None of the patients were pregnant.

A total of 83 patients had vaginal cultures to study the effect ofvaginosis on vaginal pH.

Two hundred one patients were tested for vaginal pH, serum FSH and serumestradiol. Of these 201 patients, 100 were on Estrogen ReplacementTherapy and 8 were on oral contraceptives. Ninety-three patients were onno hormonal treatment. No patients tested were using vaginal medication.

Eighteen patients were tested for vaginal pH, serum FSH and serumestradiol on two separate occasions. Nine of these patients were testedbefore and after the use of estrogen. Nine patients were tested after achange in estrogen dose. In all nine cases, the estrogen does wasincreased. This separate study was done to observe the change in vaginalpH, serum FSH and serum estradiol in response to a change in estrogentherapy.

Phenaphthazine (NITRAZINE®) pH indicator paper was used for vaginal pHtesting (NITRAZINE® pH indicator paper pH 4.5 to 7.5 range, distributedby APOTHECON®, a Bristol-Myers Squibb Company, Princeton, N.J.). This pHpaper has been used for vaginal pH testing since 1938. The extendedrange of pH 4.5 to 7.5 proved to be easier to read and morecomprehensive for vaginosis and vaginal estrogen level. Other pH testingpapers were tried. (Hydrion® pH papers, Micro Essential Laboratory, 4224Avenue H, Brooklyn, N.Y. 11210 (718) 338-3618). (ColorpHast® pH teststrips, EM Science, 480 Democrat Road, Gibbstown, N.J. 08027 (800)222-0342).

The pH paper was applied directly to the lateral vaginal wall at theouter third of the vagina. Care was taken to avoid cervical mucous (pH7.0), blood (ph 7.4), or other substances (such as semen pH 7.0-8.0) andlubricating jelly known to affect vaginal pH. All samples wereinterpreted in incandescent light for accuracy.

All vaginal cultures were collected using the Star Swab, StarplexTransport System and were sent to Unilab Corporation, Tarzana, Calif.Venopuncture for blood samples was obtained within one hour of thevaginal pH test. Serum FSH was run on the Dade/Baxter, Inc. Stratus IIautomated instrument and reported as miU/mL. Female normal ranges are:Follicular Phase: 3.6-16.0 miU/ml, Mid Cycle Peak: 8.1-28.9 miU/ml,Luteal Phase: 1.8-11.7 miU/mL and Post Menopausal: 22.9-167.0 miU/mL.Serum estradiol was determined by radio immune assay, using DiagnosticsProducts Corporation's Coat A Count and reported as pg/mL. The normalrange is 10-375. All tests were done at Huntington Memorial Hospitallaboratory, Pasadena, Calif. Statistical analysis was performed by usingthe computer program "Statistical Package for Social Sciences" (SPSS).

Relationships between vaginal pH, serum estradiol and FSH levels wereevaluated using Spearmans's Correlation Coefficients. Treated anduntreated groups were compared for these variables using t-tests andANOVA with Duncan Multiple Comparisons. Paired t-tests were used tocompare the difference in means due to initiation or change of estrogentherapy.

RESULTS:

Of 84 patients who had vaginal cultures, 27 grew normal flora, 14 yeast,15 Beta-hemolytic-streptococcus, 14 gardnerella, and 13 mixed pathogens.The mean pH of three subgroups with bacterial vaginosis is significantlyhigher than that obtained in patients with either normal flora or yeastinfection (One way ANOVA, p<0.05). There was no significant differencein the vaginal pH among the three subgroups with bacterial vaginosis,and there was no significant difference between the pH in patients withyeast infection and those with normal flora.

In the overall group of 201 women tested for vaginal pH, estradiol andFSH, vaginal pH correlated positively with serum FSH levels andnegatively with serum estradiol using Spearman's correlationcoefficients.

When the group of 201 women was divided into those on estradiol therapyand those on no treatment, significant differences were found betweenmean vaginal pH, serum estradiol levels, and serum FSH levels. Thesedifferences were significant despite the inclusion of some apparentlynormally cycling women in the untreated group. There was no significantdifference in the mean age of the patients between the two groups.

The characteristics of 18 women studied both before and after initiation(n=9) or change (n=9) of estrogen replacement therapy showed that serumestradiol levels increased and FSH levels decreased significantly afterinitiation or changes of dose of ERT (p<0.003 and p<0.001 respectively,using paired t-testing). There was a significant decrease in vaginal pHfrom 6.1±0.7 to 4.6±0.3 (p<0.001) in the group who went from notreatment to estrogen replacement. Mean vaginal pH also decreased,although to a lesser degree of significance, in the women who went fromlower dose to higher dose ERT (p=0.05).

The data obtained support the well documented body of literatureindicating that vaginosis results in an elevated vaginal pH (5.0-6.5).For this reason alone, vaginal pH should become a routine test duringmost speculum examinations. Women should be encouraged to do vaginal pHtesting to alert both pregnant and non-pregnant women to the possibilityof sub-clinical vaginosis and to seek medical advice for properdiagnosis and treatment. The combination of pH testing, vaginal culture,and treatment as indicated, have shown a decrease in premature ruptureof membranes and premature delivery.

The editorial comments of Watson A. Bowes, Jr. in the May 1996 issue ofObstetrical and Gynecological Survey are pertinent.

Statistically significant is the fact that the vaginal pH level, in theabsence of vaginosis, is a reasonable marker for most patient'sestradiol status. In addition, an elevated vaginal pH level in a wellestrogenized patient is a reasonable marker for vaginosis. In thisregard, detected pH correlates positively (directly) with FSH; and pHcorrelates negatively (inversely) with estradiol intake.

In consideration of all that as been said, vaginal and/or urethraltesting for pH level appears to be that hoped for, reliable, "low-tech"tool. It certainly complies with the mandate for cost-effective,improved health care.

In the above, estrogen or estradiol can be administered orally,intermuscularly, or vaginally.

I claim:
 1. In the method of detecting pathogenic bacteria in thevagina, the steps that includea) providing a vaginal moisture receiverreceivable into the vagina, b) providing a reactant which changes colorwhen contacted by moisture containing pathogenic bacteria, c) receivingvaginal moisture on the receiver, d) and contacting said reactant withvaginal moisture on the receiver, and receiver maintained substantiallycompletely outwardly exposed to contact with said moisture and reagent,e) and detecting a change in color at the receiver that indicates thepresence of pathogenic bacteria.
 2. The method of claim 1 wherein saidreceiver is in the form of a swab.
 3. The method of claim 1 wherein saidreactant is carried by the receiver.
 4. The method of claim 1 whereinsaid reactant comprises potassium hydroxide.
 5. The method of claim 1including manipulating said receiver to control said contacting of thereactant with vaginal moisture on the receiver.
 6. The method of claim 1including manipulating said reactant to control said contacting of thereactant with vaginal moisture on the receiver.
 7. The method of claim 5wherein said receiver is provided in the form of a swab.
 8. The methodof claim 7 including providing a stick on which the swab is carried, thestick being manipulated to manipulate the swab to control saidcontacting.
 9. The method of claim 6 wherein the receiver is provided inthe form of a swab.
 10. The method of claim 9 including providing astick on which the swab is carried.
 11. The method of claim 9 includingbringing the reactant into contact with the swab to effect saidcontacting.
 12. The method of claim 1 wherein said contacting iseffected by bringing the reactant into contact with the receiver. 13.The method of claim 12 wherein reactant is caused to flow into contactwith the receiver.
 14. The method of claim 12 wherein the reactant issprayed into contact with the receiver.
 15. The method of claim 12wherein the reactant is placed into contact with the receiver.
 16. Themethod of claim 1 wherein the reactant is provided in flowable form in acontainer, and wherein the reactant is caused to flow from the containerinto contact with the receiver.
 17. The method of claim 1 includinga)providing an elongated carrier and a flexible outer container supportedon the carrier, b) providing said receiver on the carrier to communicatewith the interior of said outer container, c) providing a frangibleinner container protectively located within the outer container, andproviding flowable aqueous alkaline fluid reactant within the innercontainer, d) and exerting pressure on the outer container sufficient torupture the inner container, thereby releasing the reactant into theinterior of the outer container to enable reactant fluid flow to saidreceiver for reaction with bacteria containing vaginal moisture on thereceiver.
 18. The method of claim 17 wherein said aqueous alkaline fluidreactant consists essentially of a dilute aqueous solution of potassiumhydroxide.
 19. The method of claim 18 wherein said solution consists of10 to 20% potassium hydroxide.
 20. The method of claim 1 wherein saidouter container is provided in relatively close association with saidreceiver in the form of a swab.
 21. The method of claim 20 wherein saidouter container is provided at a location on the carrier that isrelatively remote from the swab.
 22. The method of claim 21 includingproviding a duct associated with the carrier to convey fluid reactantfrom the container interior to the swab.
 23. The method of claim 17wherein said pressure is exerted manually.
 24. The method of claim 17including manipulating said carrier to cause endwise and sidewise forceexertion on the receiver in the form of a swab to cause the swab toabsorb vaginal moisture, in the vagina.
 25. The method of claim 1 alsoincluding providing a pH detection means for detection of vaginalmoisture pH in conjunction with performing the steps of claim
 1. 26. Themethod of claim 25 including providing a carrier for the receiver, andwherein said pH detection means is provided at a location on thecarrier.
 27. The method of claim 25 including locating said pH detectionmeans on a carrier for the receiver relatively remotely from saidreceiver in the form of a swab.
 28. The method of claim 23 includingcontrolling said manual pressure to control reactant fluid flow to theswab.
 29. Apparatus for detecting pathogenic bacteria in the vagina,comprisinga) a vaginal moisture receiver receivable into the vagina, b)a reactant which changes color when contacted by moisture containingpathogenic bacteria, c) the reactant positioned for contact with vaginalmoisture on the receiver, and the receiver maintained substantiallycompletely outwardly exposed for contact with said moisture, d) thereceiver characterized as exhibiting a change in color that indicatesthe presence of pathogenic bacteria.
 30. The apparatus of claim 29wherein said receiver is in the form of a swab.
 31. The apparatus ofclaim 29 wherein said reactant is carried by the receiver.
 32. Theapparatus of claim 29 wherein said reactant comprises potassiumhydroxide.
 33. The apparatus of claim 29 including means formanipulating said receiver to control said contacting of the reactantwith vaginal moisture on the receiver.
 34. The apparatus of claim 29including means for manipulating said reactant to control saidcontacting of the reactant with vaginal moisture on the receiver. 35.The apparatus of claim 33 wherein said receiver is provided in the formof a swab.
 36. The apparatus of claim 35 including a stick on which theswab is carried, the swab manipulable by the stick to control saidcontacting.
 37. The apparatus of claim 29 wherein reactant is positionedproximate the receiver to flow into contact with the receiver.
 38. Theapparatus of claim 29 wherein the reactant is contained by a spraydevice to be sprayed into contact with the receiver.
 39. The apparatusof claim 29 wherein the reactant is in contact with the receiver. 40.The apparatus of claim 29 including:i) an elongated carrier carryingsaid receiver, ii) and an elongated receptacle into which said carrieris endwise receivable, for storage.
 41. The apparatus of claim 40including at least one color comparison measurement element on saidreceptacle to be visible from the exterior.
 42. The apparatus of claim41 including a window on the receptacle in proximity to said at leastone color comparison measurement element, and through which saidreceiver is visible.
 43. The apparatus of claim 42 wherein multiple ofsaid color comparison measurement elements are provided, proximate saidwindow and located in series lengthwise of the window.
 44. The apparatusof claim 40 wherein said carrier and receptacle have interfittingrelation.